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1.
Cancer Cell Int ; 16: 40, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27252596

RESUMO

[This retracts the article DOI: 10.1186/s12935-014-0154-0.].

2.
Cancer Cell Int ; 15: 18, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25745359

RESUMO

OBJECTIVE: Psoriasin (S100A7) plays a role in the malignant potential of several epithelial cancers, and could candidate diagnostic marker or therapeutic target. Nuclear factor kappa B (NF-κB) regulates cancer cell growth and is modulated by phospholipase activity in many cancer cells. In the present study, we first evaluate the involvement of S100A7 in lung squamous cell carcinoma and its clinical usefulness for diagnosis. We then study whether knockdown of S100A7 in lung squamous cell carcinoma cells would reduce cell proliferation and NF-κB activity in vitro and attenuate tumor growth in vivo. METHODS: We examined S100A7 expression in lung squamous cell carcinoma tissues by immunohistology. The human lung squamous cell carcinoma cell line NCI-H520 were transduced with short hairpin RNA targeting S100A7. Quantitative reverse transcriptase-polymerase chain reaction and immunoblotting confirmed knockdown of S100A7 messenger RNA and protein, respectively. Cell proliferation was evaluated by the MTT assay. NF-κB phosphorylation was assayed by western blot. 1 × 10(6) of NCI-H520/S100A7 knockdown cells were injected into the left flanks of nude mice (aged 6 to 8 weeks). Tumors were followed for 35 days, then removed and stained with hematoxylin and eosin, stained with Ki-67, and analyzed for S100A7 protein expression. RESULTS: S100A7 protein levels were significantly higher in carcinoma specimens than in nonneoplastic tissues. S100A7 might be a useful marker for diagnosis of lung squamous cell carcinoma. In vitro data showed that inhibition of S100A7 decreased proliferation of NCI-H520 cells. S100A7 knockdown reduced NF-κB phosphorylation and tumor growth in vivo and vivo. Explanted knockdown tumors maintained lower S100A7 levels compared with wild-type, confirmed by immunohistology. Ki-67 staining was more prominent throughout the wild-type tumors compared with knockdown tumors. CONCLUSIONS: Our present results suggest that S100A7 level is a promising tool for diagnosis of lung squamous cell carcinoma. Knockdown of S100A7 suppresses lung cancer growth in part by attenuating NF-κB activity. S100A7 may be a promising therapeutic target for lung squamous cell carcinoma.

3.
Zhongguo Dang Dai Er Ke Za Zhi ; 17(2): 168-71, 2015 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-25760843

RESUMO

OBJECTIVE: To study the relationship between loss of sex chromosomes and prognosis in children with acute myeloid leukemia (AML) M2 subtype. METHODS: According to cytogenetic characteristics, 106 children with AML were divided into three groups: patients with normal karyotype (Group A, n=26), patients with abnormal karyotype who had no loss of sex chromosomes (Group B, n=52), and patients with abnormal karyotype who had loss of sex chromosomes (Group C, n=28). Prognosis was compared between the three groups. RESULTS: The 5-year event-free survival (EFS) rates of Groups A, B, and C were (38.9±11.2)%, (59.3±7.3)%, and (66.5±10.5)%, respectively; the EFS of Group C was significantly higher than that of Group A (P=0.035). The 5-year overall survival (OS) rates of Groups A, B, and C were (54.3±13.5)%, (68.1±7.7)%, and (77.9±9.8)%, respectively (P>0.05). The 5-year EFS of 58 patients with t(8;21) was (63.3±7.3)%, significantly higher than that of patients with normal karyotype (P=0.015). All the 28 cases in Group C had t(8;21), and their 5-year EFS was not significantly different from that of patients with t(8;21) in Group B (P>0.05). CONCLUSIONS: Loss of sex chromosomes is a favorable karyotype in children with AML M2 subtype and the patients in this group mostly have t(8;21). Why loss of sex chromosomes indicates a favorable prognosis is probably because it is accompanied by t(8;21) in the patients.


Assuntos
Leucemia Mieloide Aguda/genética , Aberrações dos Cromossomos Sexuais , Adolescente , Criança , Pré-Escolar , Cromossomos Humanos Par 21 , Cromossomos Humanos Par 8 , Feminino , Humanos , Cariótipo , Leucemia Mieloide Aguda/mortalidade , Masculino , Prognóstico , Translocação Genética
4.
Zhongguo Dang Dai Er Ke Za Zhi ; 16(5): 494-8, 2014 May.
Artigo em Chinês | MEDLINE | ID: mdl-24856999

RESUMO

OBJECTIVE: To study the changes of minimal residual disease (MRD) in children with B cell acute lymphoblastic leukemia (B-ALL) of different genetic abnormalities. METHODS: Between February 2004 and April 2013, 271 newly diagnosed B-ALL pediatric patients who had finished the induction chemotherapy were enrolled in the study. The characteristics of changes in MRD in patients with different genetic abnormalities on the 15th day and at the end of the induction therapy were analyzed. RESULTS: On the 15th day of the induction chemotherapy, the MRD positive proportion in patients with hyperdiploid was higher on all the three cut-off levels of MRD≥0.1%, 1% and 10% compared to patients without hyperdiploid (P<0.05), but there was no significant difference in the MRD positive proportion on the three levels of MRD between the TEL-AML1-positive and TEL-AML1-negative groups (P>0.05). On the end of induction chemotherapy, there was no significant difference in the MRD positive proportion on the three levels of MRD between the patients with and without hyperdiploid (P>0.05), neither between the BCR-ABL-positive and negative groups. The MRD positive proportion in TEL-AML1-negative patients was significantly higher than in TEL-AML1-positive patients on all three levels of MRD (P<0.05). The MRD positive proportion on two levels of MRD≥0.01% and 0.1% in E2A-PBX1-negative patients was significantly higher than in E2A-PBX1-positive patients (P<0.05). CONCLUSIONS: Children with B-ALL of different genetic abnormalities have different MRD levels during, and at the end of, induction therapy. The prognostic significance of MRD may be related to the genetic abnormalities.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Quimioterapia de Indução , Lactente , Recém-Nascido , Masculino , Neoplasia Residual/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
5.
J Alzheimers Dis ; 39(2): 239-51, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24150104

RESUMO

Rosiglitazone has been known to attenuate neurodegeneration in Alzheimer's disease (AD), but the underlying mechanisms remain to be fully elucidated. In this study, living-cell image, immunocytochemistry, and electrophysiology were used to examine the effects of soluble amyloid-ß protein (Aß) oligomers and rosiglitazone on the synapse formation, plasticity, and mitochondrial distribution in cultured neurons. Incubation of hippocampal cultures with amyloid-ß (Aß)42 oligomers (0.5 µM) for 3 h significantly decreased dendritic filopodium and synapse density. Pretreatment with rosiglitazone (0.5-5 µM) for 24 h prevented the Aß42-induced loss of dendritic filopodium and synapse in a dose-dependent manner. However, neither Aß42 oligomer nor rosiglitazone has a significant effect on the velocity and length of dendritic filopodia. Electrophysiological recording showed that acute exposure of slices with 0.5 µM Aß42 oligomers impaired hippocampal long-term potentiation (LTP). Pre-incubation of hippocampal slices with rosiglitazone significantly attenuated the Aß42-induced LTP deficit, which depended on rosiglitazone concentrations (1-5 µM) and pretreatment period (1-5 h). The beneficial effects of rosiglitazone were abolished by the peroxisome proliferator-activated receptor gamma (PPARγ) specific antagonist, GW9662. Moreover, the mitochondrial numbers in the dendrite and spine were decreased by Aß42 oligomers, which can be prevented by rosiglitazone. In conclusion, our data suggested that rosiglitazone prevents Aß42 oligomers-induced impairment via increasing mitochondrial numbers in the dendrite and spine, improving synapse formation and plasticity. This process is most likely through the PPARγ-dependent pathway and in concentration and time dependent manners. The study provides novel insights into the mechanisms for the protective effects of rosiglitzone on AD.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Mitocôndrias/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Nootrópicos/farmacologia , Fragmentos de Peptídeos/toxicidade , Tiazolidinedionas/farmacologia , Anilidas/farmacologia , Animais , Células Cultivadas , Fármacos do Sistema Nervoso Central/farmacologia , Dendritos/efeitos dos fármacos , Dendritos/patologia , Dendritos/fisiologia , Espinhas Dendríticas/efeitos dos fármacos , Espinhas Dendríticas/patologia , Espinhas Dendríticas/fisiologia , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Hipocampo/fisiopatologia , Técnicas In Vitro , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/fisiologia , Masculino , Mitocôndrias/patologia , Mitocôndrias/fisiologia , Plasticidade Neuronal/fisiologia , Neurônios/patologia , Neurônios/fisiologia , PPAR gama/antagonistas & inibidores , PPAR gama/metabolismo , Ratos , Ratos Wistar , Rosiglitazona , Sinapses/efeitos dos fármacos , Sinapses/patologia , Sinapses/fisiologia , Fatores de Tempo
6.
Int J Clin Exp Pathol ; 7(11): 8279-89, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25550886

RESUMO

OBJECTIVE: S100A7 plays a role in the malignant potential of several epithelial cancers, and could candidate diagnostic marker or therapeutic target. Nuclear factor kappa B (NF-κB) regulates cancer cell growth and is modulated by phospholipase activity in many cancer cells. In the present study, we first evaluate the involvement of S100A7 in lung squamous cell carcinoma and its clinical usefulness for diagnosis. We then study whether knockdown of S100A7 in lung squamous cell carcinoma cells would reduce cell proliferation and NF-κB activity in vitro and attenuate tumor growth in vivo. METHODS: We examined S100A7 expression in lung squamous cell carcinoma tissues by immunohistology .The human lung squamous cell carcinoma cell line NCI-H520 were transduced with short hairpin RNA targeting S100A7. Quantitative reverse transcriptase-polymerase chain reaction and immunoblotting confirmed knockdown of S100A7 messenger RNA and protein, respectively. Cell proliferation was evaluated by the MTT assay. NF-κB phosphorylation was assayed by western blot. 1×10(6) of NCI-H520/S100A7 knockdown cells were injected into the left flanks of nude mice (aged 6 to 8 weeks). Tumors were followed for 35 days, then removed and stained with hematoxylin and eosin, stained with Ki-67, and analyzed for S100A7 protein expression. RESULTS: S100A7 protein levels were significantly higher in carcinoma specimens than in nonneoplastic tissues. S100A7 might be a useful marker for diagnosis of lung squamous cell carcinoma. In vitro data showed that inhibition of S100A7 decreased proliferation of NCI-H520 cells. S100A7 knockdown reduced NF-κB phosphorylation and tumor growth in vivo and vivo. Explanted knockdown tumors maintained lower S100A7 levels compared with wild-type, confirmed by immunohistology. Ki-67 staining was more prominent throughout the wild-type tumors compared with knockdown tumors. CONCLUSIONS: Our present results suggest that S100A7 level is a promising tool for diagnosis of lung squamous cell carcinoma. Knockdown of S100A7 suppresses lung cancer growth in part by attenuating NF-κB activity. S100A7 may be a promising therapeutic target for lung squamous cell carcinoma.


Assuntos
Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/patologia , Proteínas S100/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores Tumorais/análise , Western Blotting , Carcinoma de Células Escamosas/mortalidade , Proliferação de Células , Feminino , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , NF-kappa B , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Proteína A7 Ligante de Cálcio S100
7.
Eur J Haematol ; 91(6): 483-9, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24033687

RESUMO

OBJECTIVES: The efficacy of all-trans retinoic acid (ATRA) and arsenic trioxide (As2 O3 ) as induction therapy for adult acute promyelocytic leukaemia (APL) has been documented in several clinical trials. However, the role of ATRA/As2 O3 combination in induction and consolidation therapy in children remains unclear. Here, we report the efficacy of combined treatment with As2 O3 and ATRA as induction and consolidation chemotherapy to treat newly diagnosed childhood APL. METHODS: From 1998 to 2011, 43 children with newly diagnosed APL received induction and consolidation chemotherapy with ATRA and As2 O3 (Protocol B). Rates of complete remission (CR), event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) and drug toxicity were compared between children treated with Protocol B and 25 others treated previously with ATRA alone as induction chemotherapy (Protocol A). RESULTS: Of 43 patients treated with Protocol B, 41 (95.4%) achieved CR (two died of intracranial haemorrhage on day 10 and 14). In contrast, only 20 (80%) of 25 patients treated with Protocol A achieved CR. Thus, the CR rate was significantly lower in patients receiving induction chemotherapy with Protocol A than in those treated with Protocol B (P = 0.045, χ(2) = 6.508). Of the 41 patients who achieved CR on induction therapy with Protocol B, 40 also received consolidation therapy. Molecular relapse, but no overt morphological relapse, occurred in one patient at 25 months after diagnosis; this patient regained CR status with As2 O3 treatment. With a median follow-up period of 75 months, estimated EFS, DFS and OS rates were 92.5 ± 4.2%, 97.1 ± 2.9% and 95.3 ± 3.2%, respectively, for Protocol B. In contrast, with a median follow-up of 127 months, the EFS, DFS and OS rates at 75 months were 70.4 ± 9.4%, 76.4 ± 9.2% and 70.4 ± 9.4%, respectively, for Protocol A. Thus, patients treated with Protocol A showed significantly lower EFS (P = 0.021) and OS (P = 0.007) rates than those treated with Protocol B. CONCLUSIONS: Application of As2 O3 and ATRA as induction and consolidation chemotherapy resulted in excellent outcomes and improved long-term prognosis in children with newly diagnosed APL.


Assuntos
Antineoplásicos/uso terapêutico , Arsenicais/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/mortalidade , Óxidos/uso terapêutico , Adolescente , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Trióxido de Arsênio , Arsenicais/administração & dosagem , Arsenicais/efeitos adversos , Criança , Pré-Escolar , Quimioterapia de Consolidação , Feminino , Humanos , Quimioterapia de Indução , Leucemia Promielocítica Aguda/patologia , Masculino , Neoplasia Residual , Óxidos/administração & dosagem , Óxidos/efeitos adversos , Prognóstico , Resultado do Tratamento , Tretinoína/administração & dosagem , Tretinoína/efeitos adversos , Tretinoína/uso terapêutico
8.
Zhongguo Dang Dai Er Ke Za Zhi ; 15(6): 444-7, 2013 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-23791059

RESUMO

OBJECTIVE: To explore the efficacy and adverse effects of clofarabine for relapsed/refractory acute lymphoblastic leukemia in children. METHODS: Twenty-six pediatric patients with relapsed/refractory acute lymphoblastic leukemia were treated with clofarabine. There were 22 males and 4 females, with a mean age of 9.5 years (ranging from 4 to 17 years). They received clofarabine 52 mg/m2 intravenously over 2 hours daily for 5 days. Thirteen patients received two cycles and one patient received three cycles. RESULTS: In the first cycle of clofarabine, complete remission was obtained in 11 children (42%) and partial remission was obtained in 7 children (27%). Eight children (31%) were considered unresponsive. In the second cycle, 11 (85%) of the 13 children obtained complete remission, 1 (8%) partial remission and 1 (8%) was unresponsive. One child received three cycles and obtained complete remission in each cycle. The common adverse events were myelosuppression, infection, liver dysfunction and gastrointestinal adverse reactions. There were no chemotherapy-related deaths. CONCLUSIONS: Clofarabine is effective in the treatment of children with relapsed/refractory acute lymphoblastic leukemia and its adverse effects can be tolerated. Clofarabine could be a promising new treatment for relapsed/refractory acute lymphoblastic leukemia.


Assuntos
Nucleotídeos de Adenina/uso terapêutico , Antineoplásicos/uso terapêutico , Arabinonucleosídeos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Nucleotídeos de Adenina/efeitos adversos , Adolescente , Antineoplásicos/efeitos adversos , Arabinonucleosídeos/efeitos adversos , Criança , Pré-Escolar , Clofarabina , Feminino , Seguimentos , Humanos , Lactente , Masculino , Recidiva
9.
Zhonghua Xue Ye Xue Za Zhi ; 33(7): 536-40, 2012 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-22967413

RESUMO

OBJECTIVE: To investigate the expression of the Wilms' tumor 1 (WT1) mRNA in childhood myelodysplastic syndrome (MDS), and to evaluate WT1 as a tool to differentiate MDS from aplastic anemia(AA). METHODS: The quantitative expression of WT1 transcript by using real-time quantitative polymerase chain reaction (RQ-PCR) was performed in the bone marrow samples of 36 childhood MDS and 49 childhood AA, the samples were collected from September 2008 to December 2011. RESULTS: (1) The positive rate of WT1 in severe AA (SAA) was 0, 14.3% in chronic AA (CAA), 58.6% in refractory cytopenia (RC), 100% in refractory anemia with excessive blast (RAEB) and 97.5% in acute myeloid leukemia (AML). The mean level of WT1 in SAA, CAA, RC, RAEB and AML was 0.041%, 0.357%, 7.037%, 12.680% and 24.210%, respectively. The positive rate of WT1 in RC patients was higher than that of SAA (P = 0.000) and CAA (P = 0.001). (2) The positive rate of WT1 in patients with hypoplastic MDS was 66.7% and was higher than that of SAA (P = 0.000) and CAA (P = 0.001). The mean level of WT1 in patients with hypoplastic MDS was (3.022 ± 5.040)% and higher than that of SAA \[(0.041 ± 0.047)%, P = 0.000\] and CAA\[(0.351 ± 0.479)%, P = 0.002\]. CONCLUSIONS: The level of WT1 in childhood MDS was higher than that of childhood AA. The degree of WT1 expression in MDS increased during disease progression. WT1 is a useful tool for differentiating the childhood hypoplastic MDS from AA.


Assuntos
Síndromes Mielodisplásicas/metabolismo , Proteínas WT1/metabolismo , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Proteínas WT1/genética
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 13(12): 931-5, 2011 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-22172252

RESUMO

UNLABELLED: OBJECTIVE To study the clinical and biological characteristics and prognosis of t(8;21)/AML1-ETO-positive childhood acute myeloid leukemia (AML). METHODS: The clinical data of 55 children who were diagnosed as t (8; 21)/AML1-ETO-positive AML were retrospectively studied. Event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) rates were estimated by the Kaplan-Meier method. Prognostic factors were evaluated by COX regression analysis software. RESULTS: Of the 55 patients, 4 patients gave up treatment after the diagnosis was confirmed and 4 patients were lost to follow-up after the first chemotherapy course. The remaining 47 patients received a double-induction therapy. The total complete remission (CR) rate was 71% and 94% after the first and second chemotherapy course, respectively. The disease was relapsed in 10 patients (21%). The 5-year EFS, DFS and OS rates were (56.1 ± 7.9)%, (59.8 ± 8.1)%, and (72.0 ± 8.1)%, respectively. Multivariate analysis showed that age was an independent risk factor for the long-term prognosis. The older children had a greater risk of experiencing an accident or death (P<0.05). The 5-year OS rate in 27 patients with regular consolidation chemotherapy was significantly higher than 13 patients with irregular chemotherapy after CRz [(47.5 ± 17.1)% vs (38.9 ± 17.3)%; P<0.01]. CONCLUSIONS: Childhood t(8;21)/AML1-ETO-positive AML is a highly heterogeneous disease, with a high CR rate and a good long-term prognosis. Age is one of the important factors affecting the long-term therapeutic effect. Regular consolidation chemotherapy applied after CR usually is helpful.


Assuntos
Cromossomos Humanos Par 21 , Cromossomos Humanos Par 8 , Subunidade alfa 2 de Fator de Ligação ao Core/análise , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Proteínas de Fusão Oncogênica/análise , Translocação Genética , Adolescente , Exame de Medula Óssea , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Prognóstico , Proteína 1 Parceira de Translocação de RUNX1
11.
Zhongguo Dang Dai Er Ke Za Zhi ; 13(9): 718-21, 2011 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-21924019

RESUMO

OBJECTIVE: To study the clinical features and etiological spectrum of pancytopenia in children. METHODS: The clinical data of 174 children with pancytopenia between September 2003 and January 2010 were retrospectively reviewed. RESULTS: Pale face was the most common clinical manifestation (147 cases, 84.5%), followed by bleeding (87 cases, 50.0%) and fever (41 cases, 23.6%). Mild to moderate anemia, severe thrombocytopenia and mild leucopenia were common in complete blood count. Of the 174 children, pancytopenia was attributed to hematopoietic system diseases in 155 cases (89.1%) and non-hematopoietic system diseases (virus infections, systemic lupus erythematosus, hypersplenism and neuroblastoma) in 6 cases (3.4%). Aplastic anemia (91 cases, 52.3%) was the most common cause of pancytopenia, followed by myelodysplastic syndrome (37 cases, 21.3%), acute leukemia and other hematological tumours (11 cases, 6.3%) and hemophagocytic syndrome (6 cases, 3.4%). The cause of pancytopenia was not identified in 13 cases (7.5%). CONCLUSIONS: Anemia, bleeding and fever are the main clinical manifestations of pancytopenia in children. Pancytopenia is mostly caused by aplastic anemia in children. Myelodysplastic syndrome, hematological tumours and hemophagocytic syndrome are also the common causes.


Assuntos
Pancitopenia/etiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pancitopenia/sangue , Pancitopenia/diagnóstico
12.
Neurosci Lett ; 496(1): 54-9, 2011 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-21507342

RESUMO

Niemann-Pick disease type C (NPC) is a progressive neurodegenerative disorder characterized by accumulation of free cholesterol in late endosomes/lysosomes. The pathological basis for the disease has been poorly understood yet. In our previous study, we have demonstrated that synaptic function is impaired in this disease. In the current study, electrophysiological and fluorescent dyes studies were used to determine whether the synaptic defects result from presynaptic or postsynaptic contributions. Furthermore, we would like to ascertain whether such defects are caused by direct effect of NPC1 deficiency in neurons or indirect effect of NPC1 deficiency in glial cells. Both mean inter-event interval of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) were significantly larger in NPC1(-/-) neurons than those in the wild-type neurons, while the amplitudes and the receptor kinetics were not different compared with those in wild-type controls. Synaptic vesicle exocytosis was also slower in the NPC1(-/-) neurons. The mean time constant of destaining was larger in NPC1(-/-) neurons than in wild-type controls both in the presence and absence of glial cells. All these results indicated a general presynaptic functional impairment in the NPC1(-/-) neurons and such defects were not dependent of glial cells. Therefore, neuropathology characteristics of NPC diseases may be a more possible consequence of neuronal presynaptic dysfunction than indirect defects in glial cells.


Assuntos
Neuroglia/patologia , Neurônios/patologia , Terminações Pré-Sinápticas/patologia , Proteínas/metabolismo , Animais , Animais Recém-Nascidos , Células Cultivadas , Colesterol/metabolismo , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/genética , Exocitose/efeitos dos fármacos , Exocitose/genética , Filipina/metabolismo , Hipocampo/citologia , Peptídeos e Proteínas de Sinalização Intracelular , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Neurônios/efeitos dos fármacos , Proteína C1 de Niemann-Pick , Técnicas de Patch-Clamp , Cloreto de Potássio/farmacologia , Proteínas/genética
13.
Zhongguo Dang Dai Er Ke Za Zhi ; 12(3): 172-6, 2010 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-20350423

RESUMO

OBJECTIVE: To investigate whether there were differences in the clinical characteristics, cytogenetic characteristics, immunophenotype and prognosis in children with B cell type acute lymphoblastic leukemia (B-ALL) carrying different fusion genes. METHODS: The research included 80 children with B-ALL from Peking University People's Hospital between March 2006 and December 2008. Eighteen children were positive for TEL/AML1, 14 for E2A/PBX1, 11 for BCR/ABL,and 2 cases for MLL/AF4, and 35 cases were negative for all of the 4 fusion genes. Data including clinical characteristics, morphology, immunophenotype and cytogenetic characteristics were collected, and the disease-free survival (DFS) was evaluated. The children were followed up until April 2009. RESULTS: In the 18 children with TEL/AML1+B-ALL, 66.7% were younger than 5 years old. They had low tumor load. FAB-L2 morphology was commonly observed, but t(12;21) was often absence in these children. Up to now,17 children who survived were disease-free. In the 14 children with E2A/PBX1+B-ALL, the majority were female. Thirteen children showed FAB-L1 morphology. Twelve children showed pre-B-ALL immunophenotype. The EFS was close to 80%. In the 11 children with BCR/ABL+B-ALL, 10 children showed common B type immunophenotype. FAB-L1 and FAB-L2 morphology was found in 4 children respectively. The DFS was less than 20%. Two children with MLL/AF4 positive B-ALL had high tumor load. Their morphologic diagnosis was FAB-L1. Both showed the Pro-B-ALL immunophenotype. One child discontinued treatment at the early stage of chemotherapy, and the other child survived disease-free until now. CONCLUSIONS: The B-ALL children with different fusion genes have different clinical characteristics, immunophenotypes and prognosis.


Assuntos
Fusão Gênica , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Adolescente , Criança , Pré-Escolar , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Feminino , Proteínas de Homeodomínio/genética , Humanos , Imunofenotipagem , Lactente , Masculino , Proteína de Leucina Linfoide-Mieloide/genética , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 17(4): 908-12, 2009 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-19698227

RESUMO

The aim of study was to investigate the application of a novel microarray approach for the eight most common leukemia translocations in children for routine molecular diagnostic hematopathology practice. Bone marrow samples from 84 children with leukemia were analyzed by multiplex nested RT-PCR combined with oligonucleotide microarray. The results showed that out of 84 leukemic samples, 31 (36. 90%) carried 8 types of fusion genes including tel/aml1, e2a/pbx1, bcr/ablp190, bcr/ablp210, mll/af4, aml1/eto, pml/raralpha, cbfbeta/myh11. The sensitivity and specificity of the assay is comparable with the RT-PCR technique. In conclusion, this multiplex nested RT-PCR could quickly screen 8 types of chromosome structural aberrations at the same time. It can provide reliable and helpful information for risk stratification, therapy evaluation and prognosis prediction in childhood leukemia. There are both advantages and disadvantages in applying this new method. The microarray-based assay will be an effective and reliable tool in the clinical screening of leukemia patients for the presence of specific gene rearrangements with important diagnostic and prognostic implications.


Assuntos
Rearranjo Gênico , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino
15.
Zhonghua Xue Ye Xue Za Zhi ; 29(7): 454-8, 2008 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-19035177

RESUMO

OBJECTIVE: To retrospectively analyze the treatment outcomes and side effects of childhood acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) or ATRA + arsenic trioxide (As2O3). METHODS: From 1992 to 2006, 45 patients with newly diagnosed APL were enrolled. All of them were PML-RAR alpha positive. 24 patients were induced with ATRA (group A) and 21 with ATRA + As2O3 (group B). The remission rate and side effects were observed. RESULTS: 1) 19 (79.2%) patients in group A achieved CR, while 21(100%) patients in group B achieved CR. The CR rate in group A was lower than that in group B (P=0.027). 2) The recovery time of coagulation parameters and PLT count in group B was shorter than that in group A. 3) The overall survival (OS) and event-free survival(EFS) in group A were 77.8% and 66.9% at 41 months of follow-up, and in group B were 100% and 100% respectively at 34 months of followup. Group A had a significant lower EFS (P=0.0357)than group B. 4) The time of PML-RAR alpha fusion gene converting to negative in group A was longer (P=0.026) than that in group B. CONCLUSIONS: ATRA + As2O3 for patients with newly diagnosed childhood APL is a feasible treatment with higher CR rate, less side effects and longer long-term survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Arsenicais/administração & dosagem , Leucemia Promielocítica Aguda/tratamento farmacológico , Óxidos/administração & dosagem , Adolescente , Trióxido de Arsênio , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Leucemia Promielocítica Aguda/genética , Masculino , Proteínas de Fusão Oncogênica/genética , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Tretinoína/administração & dosagem
16.
Sheng Wu Gong Cheng Xue Bao ; 22(6): 950-5, 2006 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-17168318

RESUMO

The gdrA, gdrB gene coding glycerol dehydratase reactivase factor were amplified by using the genomic DNA of Klebsiella pneumoniae as the template. The gdrA and gdrB were inserted in pMD-18T to yield the recombinant cloning vector pMD-gdrAB. After the DNA sequence was determined, the gdrAB gene was subcloned into expression vector pET-28a(+) to yield the recombinant expression vector pET-28gdrAB. Under screening pressure by ampicillin and kanamycin simultaneously, the activity of glycerol dehydratase reactivase was characterized by coexpression of pET-32gldABC, which carry the gldABC gene encoding glycerol dehydratase, and pET-28gdrAB in E. coli BL21(DE3).


Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Hidroliases/genética , Hidroliases/metabolismo , Proteínas de Bactérias/isolamento & purificação , Clonagem Molecular , Eletroforese em Gel de Poliacrilamida , Escherichia coli/genética , Expressão Gênica , Vetores Genéticos/genética , Hidroliases/isolamento & purificação , Plasmídeos/genética , Reação em Cadeia da Polimerase
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 14(5): 853-7, 2006 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-17096875

RESUMO

To evaluate the significance of FCM in minimal residual disease (MRD) detection, the immunophenotyping and leukemia-associated immunophenotypes (LAIP) of leukemia cells from 273 adult and 142 childhood patients with B lineage acute lymphoblastic leukemia (B-ALL) were detected by four to six antibody combinations of 4-color CD45/SSC gating multiparametric flow cytometry (FCM). The results showed that the B-ALL patients could be classified into 4 subtypes based on different expression CD34 and CD10: subtype I (CD34(+)/CD10(-)), subtype II (CD34(+)/CD10(+)), subtype III (CD34(-)/CD10(+)), subtype IV (CD34(-)/CD10(-)). The LAIP was observed in 100% and 92% patients of subtype I and subtype II, respectively, whereas only 79.2% in subtype III. The incidence of LAIP in total B-ALL cases was 90% by using the antibodies detected in this investigation. There was no significantce different for incidence of LAIP between adult and pediatric patients. LAIP was observed in 77.6% of patients by labeling only CD34/CD10/CD19/CD45 4-color antibody combination. It is concluded that in 90% of childhood and adult B-ALL patients LAIP can be found, which suits MRD detection by multiparameter flow cytometry.


Assuntos
Linfócitos B/imunologia , Linfoma de Burkitt/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD34/análise , Linfoma de Burkitt/classificação , Linfoma de Burkitt/patologia , Linhagem da Célula , Feminino , Citometria de Fluxo/métodos , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/diagnóstico , Neprilisina/análise , Leucemia-Linfoma Linfoblástico de Células Precursoras/classificação , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
18.
Zhonghua Xue Ye Xue Za Zhi ; 27(5): 302-5, 2006 May.
Artigo em Chinês | MEDLINE | ID: mdl-16875577

RESUMO

OBJECTIVE: To evaluate the clinical significance for minimal residual disease (MRD) detection by 4 color flow cytometry in B lineage acute lymphoblastic leukemia (B-ALL). METHODS: MRD was analyzed and followed up by using two panels of 4 color antibodies, mainly CD34/CD10/CD45/CD19, in 671 consecutive bone marrow specimens and 1 cerebrospinal fluid from 98 B-ALL patients. In 26 cases of them the immunophenotyping informations at diagnosis were not available. RESULTS: Of 671 bone marrow samples, 579 were MRD negative with leukemic cells below 0.0001 and 93 were MRD positive with leukemic cells over 0.0001. Of 93 MRD positive samples, leukemic cells below 0.05 were found in 64 bone marrow samples, meanwhile in the other 29 samples leukemic cells were over 0.05. Twenty patients relapsed, 19 were bone marrow relapse and one center nerves system. Fifteen of them were found MRD positive 7 - 17 weeks before relapse including 6 patients having no immunophenotyping data at diagnosis. The percentages of leukemia cells in these 15 patients were all over 0.0001. Two relapsed patients were MRD negative in 3 and 9 months before relapse, respectively. Two relapsed after MRD monitoring stopped. If MRD level was > 0.0001 at the end of induction chemotherapy and 12 weeks of treatment, the rate of relapse was 50% (6/12), while, it was 7.5% (3/40) in MRD negative patients (P = 0.000). CONCLUSION: Relapses can be predicted by MRD monitoring, if MRD was positive in the early phase of treatment, the risk of relapse was higher. Based on the characteristics of B cells ontogeny, MRD detection can be done independently of immunophenotypic information at diagnosis.


Assuntos
Citometria de Fluxo/métodos , Neoplasia Residual/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Doença Aguda , Adolescente , Adulto , Idoso , Antígenos CD19/imunologia , Antígenos CD34/imunologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Imunofenotipagem , Antígenos Comuns de Leucócito/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/imunologia , Neprilisina/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Adulto Jovem
19.
Zhonghua Xue Ye Xue Za Zhi ; 27(5): 335-8, 2006 May.
Artigo em Chinês | MEDLINE | ID: mdl-16875586

RESUMO

OBJECTIVE: To compare the leukemia-associated immunophenotypes (LAIP) in patients with B lineage acute lymphoblastic leukemia (B-ALL) at diagnosis and relapse, and investigate its implications for minimal residual disease (MRD) detection. METHODS: The immunophenotype of leukemia cells from 410 newly diagnosed and 6 relapsed patients with B-ALL were detected by four to six antibody combination, mainly CD34/CD10/CD45/CD19 of 4-color CD45/SSC gating flow cytometry (FCM). RESULTS: The proportion of CD45 under-expressed or negative in relapsed patients was much higher than that in newly diagnosed patients, being 69.2% and 37.8% respectively. Immunophenotypic changes occurred in 9 relapsed patients (including 8 hematological relapse and 1 central nerves system relapse) when analyzed by paired samples analysis at diagnosis vs at relapse: 4 cases showed CD45 down-modulation and 2 up-modulation; 4 CD34 down-modulation and 2 CD10 up-modulation, while the expression of CD19 remained no change. MRD was observed in all 7 cases of hematological relapse 2 - 4 months before relapse, and the immunophenotype of MRD cells was the same as that in relapse. CONCLUSION: A high frequency of immunophenotypic changes occurred at relapse and even in MRD before relapse, however the accuracy of MRD monitoring seemed not affected by the FCM strategy used in this investigation.


Assuntos
Imunofenotipagem/métodos , Neoplasia Residual/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD19/imunologia , Antígenos CD34/imunologia , Criança , Pré-Escolar , Feminino , Citometria de Fluxo/métodos , Humanos , Antígenos Comuns de Leucócito/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual/diagnóstico , Neoplasia Residual/imunologia , Neprilisina/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia , Recidiva , Adulto Jovem
20.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 26(3): 202-4, 2006 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-16613260

RESUMO

OBJECTIVE: To compare the ettect and side-ettect of fluoxetine and combination of fluoxetine and Chinese or Tibetan medicine in treating senile depression in plateau district. Methods Ninety patients with diagnosis of senile depression conformed to CCMD-3 standard, in plateau district of 2260 - 3200 m altitude were randomly divided into three groups and treated with fluoxetine (group A), fluoxetine plus Sanpu Xinnao Xin granule (group B) and fluoxetine plus Xiaoyao pill (group C), respectively, 30 cases in each group. Therapeutic effects were evaluated with Hamilton' s depressive scale (HAMD) and treatment emergent symptom scale (TESS) after 6 weeks treatment. RESULTS: There was no significant difference in the therapeutic effects between the three groups. The adverse reaction in Group B and C was less than that in Group A (P<0.01). Conclusion Sanpu Xinnao Xin granule and Xiaoyao pill can raise the tolerance of patients with senile depression in plateau area against the adverse reaction of fluoxetine.


Assuntos
Transtorno Depressivo/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fluoxetina/uso terapêutico , Fitoterapia , Idoso , Altitude , Antidepressivos de Segunda Geração/uso terapêutico , Quimioterapia Combinada , Humanos , Pessoa de Meia-Idade , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico
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